The study, which included all children born in Denmark from 1994 to 2004, found that full-term neonates exposed to jaundice had as much as an 88% increased risk of being diagnosed with a psychological development disorder compared with unexposed neonates.

"The knowledge that jaundice is associated with autism is one more clue to the puzzle towards finding its etiology," lead author Rikke Damkjaer Maimburg, MPH, PhD, from Aarhus University, in Denmark, told Medscape Medical News. "If children with autism are genetically disposed to develop autism, there might be overlaps in the etiology between autism and jaundice. If exposure to jaundice can give autism, then we need to look at our treatment procedures."

Their results were published online October 11 in Pediatrics.

Link With Hyperbilirubinemia

Dr. Maimburg and colleagues decided to explore the association between neonatal jaundice, autistic disorders, and other psychological development problems after noticing in an earlier study that children later diagnosed with autism were twice as likely to be admitted to neonatal intensive care units as children without autism, even after controlling for low birth weight, malformations, preterm birth, and low Apgar scores.

"I wondered why, after controlling for all the risk factors for being admitted to the neonatal ward, that this occurred. Then I found out that the most common reason for being readmitted was because of hyperbilirubinemia," Dr. Maimburg told Medscape Medical News.Neonatal jaundice is seen in 60% of term infants and, in most cases, resolves within the first week of life. However, prolonged exposure to high bilirubin levels is neurotoxic and can cause lifelong developmental problems.

The investigators determined jaundice exposure status and diagnoses of disorders of psychological development in 733,826 children. They found that the excess risk of developing a psychological development disorder after exposure to jaundice as a neonate was between 56% (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.05 - 2.30) and 88% (HR, 1.88; 95% CI, 1.17 - 3.02).

The excess risk for infantile autism was 67% (HR, 1.67; 95% CI, 1.03 - 2.71). This risk was higher for children of parous women (HR, 2.71; 95% CI, 1.57 - 4.66) and for children born between the months of October and March (HR, 2.21; 95% CI, 1.24 - 3.94).

The risk for infantile autism disappeared if the child was conceived by a primiparous woman (HR, 0.58; 95% CI, 0.18 - 1.83) or was born between April and September (HR, 1.02; 95% CI, 0.41 - 2.50), and similar risk patterns were noted for the entire spectrum of autistic disorders.

Dr. Maimburg said that physicians should tell parents that jaundice, for the most part, is a normal condition but also advise them about ways to prevent the development of hyperbilirubinemia, and instruct them on when to contact health professionals. "I hope that this study will promote more research into jaundice and child development," she added.Screen More Carefully

Asked to comment on this study, Susan Levy, MD, from Children's Hospital of Philadelphia, Pennsylvania, and a member of the Center for Autism Research at the hospital, said she thought it was well-done.

"The population they were using gives a unique opportunity because the population is so large, and it is also self-contained, so they can track a number of different outcomes," Dr. Levy noted. "By having such a big population, they can look at a number of factors more quickly than in a prospective study, or even a retrospective study."

Dr. Levy, who is also a member of the American Academy of Pediatrics subcommittee on autism, added: "I hope that the impact of this study will result in the addition of term babies with hyperbilirubinemia to a higher risk group of children who need to be screened more carefully."

Dr Maimburg and Dr Levy have disclosed no relevant financial relationships.Pediatrics. Published online October 11, 2010.Authors and DisclosuresJournalistFran Lowryis a freelance writer for Medscape.